The theme of this program project is that the fundamental cause of asthma is inflammation of the small airways. It is an interdisciplinary study bringing together basic scientists in immunology and physiology with clinical investigators in allergy and pulmonary medicine. The aim of this program project is to define the fundamental mechanisms of the inflammatory process that causes asthma, why this inflammatory process develops in the small airways of asthmatic subjects in contrast to nonasthmatic allergic subjects, and how the inflammation of the small airways leads to the mechanical changes in the lungs of asthmatics that causes airways hyperresponsiveness and symptoms. Project 1. Mechanics of Airways Hyperresponsiveness and Asthma, studies the mechanical properties of the respiratory system of subjects with asthma and attempts to determine the mechanical basis of asthma and airways hyperresponsiveness. Measurements of physiologic function of the entire respiratory system will be compared with physiologic measurements made in the small airways of human subjects through a wedged bronchoscope. Project 2. Assessment of Inflammatory Parameters in Asthma, will study the role of mediators, cytokines, and specific cells involved in the inflammatory process of asthma. Particular attention will be paid to the role of the lymphocyte, eosinophil, basophil, and mast cell. Project 3. Mechanisms of Eosinophil and Basophil Recruitment, focuses on the mechanisms by which human eosinophils and basophils are activated and recruited to the sites of allergic inflammation. Project 4. Neurogenic Mechanisms of Airway Inflammation is an attempt to define the characteristics of airway inflammation evoked by stimulation of tachykinin containing C-fibers in the airways and how the neurogenic inflammation leads to hyperirritability. These studies use the guinea pig, but some in vitro studies are carried out on human tissues. The Bronchoscopy Core carries out the physiologic measurements made at the time of bronchoscopy on subjects of Project 1 and they provide cells and fluids from bronchoalveolar lavage for the studies of Projects 2 and 3.